miR-1290 inhibits chordoma cell proliferation and invasion by targeting Robo1.
miR-1290 inhibits chordoma cell proliferation and invasion by targeting Robo1.
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miR-1290通过靶向Robo1抑制脊索瘤细胞增殖和侵袭
DOI：
10.21037/tcr.2019.03.13
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发表时间：
2019-04
影响因子：
0.9
通讯作者：
Chen K
中科院分区：
文献类型：
--
作者：
Wang B;Zhang K;Chen H;Lu J;Wu G;Yang H;Chen K
研究背景脊索瘤是一种低级别侵袭性骨肿瘤，局部复发率高。据报道，microRNAs(MiRNAs)在脊索瘤的发生发展中起着关键作用。我们先前的研究表明miR-1290与肌肉侵袭和脊索瘤的预后有关。然而，miR-1290在脊索瘤中的潜在机制仍不清楚。本研究旨在探讨miR-1290在脊索瘤生物学行为中的作用。方法对苏州大学第一附属医院16例脊索瘤标本和10例胎儿髓核标本进行miR-1290和Robo1检测。利用生物信息学分析和荧光素酶报告基因分析验证miR-1290与脊索瘤靶基因Robo1的相互作用。体外克隆形成和Transwell法检测miR-1290表达对脊索瘤细胞增殖和侵袭能力的影响。探讨了miR-1290和Robo1在U-CH1细胞系中促进脊索瘤细胞增殖和侵袭的可能机制。结果体外功能分析表明，miR-1290过表达可显著抑制脊索瘤细胞的增殖和侵袭。生物信息学分析显示，Robo1是miR-1290的潜在靶点，荧光素酶报告实验证明，在U-CH1细胞中，miR-1290与Robo1基因之间存在关联。免疫组织化学(IHC)进一步证实Robo1在脊索瘤组织中表达上调，其表达与miR-1290在脊索瘤组织中的表达呈负相关。此外，我们还发现miR-1290的下调可以诱导脊索瘤细胞中Robo1的表达，而miR-1290的表达上调可以抑制脊索瘤细胞中Robo1的表达。结论miR-1290通过负调控Robo1基因抑制脊索瘤细胞的增殖和侵袭。
Background Chordoma is a low-grade aggressive bone tumor with a high local recurrence. MicroRNAs (miRNAs) have been reported to play crucial roles in the development of chordoma. Our previous study has shown miR-1290 is associated with muscle invasion and the prognosis of chordoma. However, the underlying mechanism of miR-1290 in chordoma remains unclear. In this study, we aimed to explore the function of miR-1290 in the biological behaviors of chordoma. Methods Sixteen sacral chordoma samples and 10 fetal nucleus pulposus specimens were collected for the detection of miR-1290 and Robo1 at the First Affiliated Hospital of Soochow University. Bioinformatic analysis and a luciferase reporter assay was used to verify the interaction between miR-1290 and the target gene robo1 in chordoma. Effects of miR-1290 expression on chordoma cell proliferation and invasion were explored by clone formation and Transwell assay in vitro. The underlying mechanisms of miR-1290 and Robo1 in chordoma cell proliferation and invasion were also explored in the U-CH1 cell line. Results In vitro functional analysis, including clone formation, and Transwell assays indicated overexpression of miR-1290 significantly suppressed chordoma cell proliferation and invasion. Bioinformatic analysis revealed Robo1 as a potential target of miR-1290, and luciferase reporter assays demonstrated the association between miR-1290 and the Robo1 gene in U-CH1 cells. Robo1 was further confirmed to be up-regulated in chordoma tissues by immunohistochemistry (IHC), which is negatively correlated with miR-1290 expression in chordoma tissue. Additionally, we found down-regulation of miR-1290 could induce the expression of Robo1 in chordoma cells, while the elevation of miR-1290 expression could inhibit Robo1 expression in chordoma cells. Conclusions miR-1290 inhibits chordoma cell proliferation and invasion by negatively regulating the Robo1 gene.